title: A common biological basis of obesity and nicotine addiction.
abstract: Smoking influences body weight such that smokers weigh less than non-smokers and smoking cessation often leads to weight increase. The relationship between body weight and smoking is partly explained by the effect of nicotine on appetite and metabolism. However, the brain reward system is involved in the control of the intake of both food and tobacco. We evaluated the effect of single-nucleotide polymorphisms (SNPs) affecting body mass index (BMI) on smoking behavior, and tested the 32 SNPs identified in a meta-analysis for association with two smoking phenotypes, smoking initiation (SI) and the number of cigarettes smoked per day (CPD) in an Icelandic sample (N=34,216 smokers). Combined according to their effect on BMI, the SNPs correlate with both SI (r=0.019, P=0.00054) and CPD (r=0.032, P=8.0 × 10(-7)). These findings replicate in a second large data set (N=127,274, thereof 76,242 smokers) for both SI (P=1.2 × 10(-5)) and CPD (P=9.3 × 10(-5)). Notably, the variant most strongly associated with BMI (rs1558902-A in FTO) did not associate with smoking behavior. The association with smoking behavior is not due to the effect of the SNPs on BMI. Our results strongly point to a common biological basis of the regulation of our appetite for tobacco and food, and thus the vulnerability to nicotine addiction and obesity.
authors.affiliation: Decode genetics/AMGEN, Sturlugata 8, Reykjavik, Iceland.
authors.forename: T E
authors.initials: TE
authors.lastname: Thorgeirsson
authors.forename: D F
authors.initials: DF
authors.lastname: Gudbjartsson
authors.forename: P
authors.initials: P
authors.lastname: Sulem
authors.forename: S
authors.initials: S
authors.lastname: Besenbacher
authors.forename: U
authors.initials: U
authors.lastname: Styrkarsdottir
authors.forename: G
authors.initials: G
authors.lastname: Thorleifsson
authors.forename: G B
authors.initials: GB
authors.lastname: Walters
authors.forename: H
authors.initials: H
authors.lastname: Furberg
authors.forename: P F
authors.initials: PF
authors.lastname: Sullivan
authors.forename: J
authors.initials: J
authors.lastname: Marchini
authors.forename: M I
authors.initials: MI
authors.lastname: McCarthy
authors.forename: V
authors.initials: V
authors.lastname: Steinthorsdottir
authors.forename: U
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.forename: K
authors.initials: K
authors.lastname: Stefansson
mesh_terms: D017668:Age of Onset; D016739:Behavior, Addictive / Q000235:genetics; D015992:Body Mass Index; D006801:Humans; D007055:Iceland / Q000453:epidemiology; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000453:epidemiology / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000235:genetics*